efficacy and safety evaluation of u01(sscart-19) in b-cell lymphoma

Conditions: B Cell Lymphoma

Summary: this is an open-label phase1 study to assess the safety and efficacy of u01(sscart-19) cell therapy in the treatment of patients with refractory or recurrent b-cell lymphoma .

cytokine release syndrome (crs) and immune effector cell-associated neurotoxicity syndrome (icans) are critical complications in car t-cell therapy. research highlights il-6 as a central driver of crs, as activated car t-cells secrete this cytokine, which in turn stimulates monocytes to produce additional il-6. to mitigate this risk, sscart-19-a modified anti-cd19 car t-cell therapy-incorporates small hairpin rna (shrna) technology to silence the il-6 gene, thereby reducing il-6 secretion by both car t-cells and monocytes. this study aims to assess the safety and efficacy of the u01 (sscart-19) therapy in patients with refractory or recurrent b-cell lymphoma .

Eligibility criteria:
inclusion criteria: 1. participants must voluntarily sign the informed consent form (icf) and demonstrate good compliance. 2. participants must meet the following requirements: 1. age ≥2 years and ≤75 years at the time of signing the icf (both sexes eligible). for minors (\<18 years), the legal guardian must sign after full disclosure; minors with decision-making capacity must co-sign with their guardians. 2. confirmed diagnosis of b-cell lymphoma according to the nccn clinical practice guidelines for b-cell lymphomas (3rd edition, 2024) . 3. prior treatment requirements : failure to achieve partial response (pr) after first-line therapy, or relapse within 12 months post-first-line therapy; relapsed/refractory b-cell lymphoma after second-line therapy (one standard chemotherapy regimen + one salvage regimen). prior treatments must include cd20 monoclonal antibody (unless cd20-negative tumor confirmed by the investigator) and anthracycline-based regimens . additionally, meet one of the following: i. ineligible for autologous stem cell transplantation (asct); ii. refusal of asct; iii. post-asct relapse. d) refractory/relapsed status at screening: relapse: disease progression (pd) after achieving pr or complete response (cr); refractory: i. no response to last-line therapy (pd during/after treatment, or stable disease \[sd\] lasting \<6 months); ii. post-asct relapse/pd (biopsy-confirmed), including relapse/pd within 12 months post-asct with sd/pd after salvage therapy2. 3. cd19 positivity confirmed by immunohistochemistry (ihc) of tumor tissue (preferably within 6 months). 4. at least one measurable lesion assessed by the lugano lymphoma response criteria (cheson 2014) . 5. ecog performance status score 0-3 . 6. adequate bone marrow reserve at screening: absolute lymphocyte count (alc) ≥0.3×10⁹/l ; platelet count (plt) ≥30×10⁹/l . 7. adequate organ function: ast/alt ≤3×uln (≤5×uln if due to tumor infiltration); total bilirubin ≤2×uln (≤3×uln for gilbert syndrome with direct bilirubin ≤1.5×uln); serum creatinine ≤1.5×uln or creatinine clearance ≥60 ml/min (cockcroft-gault formula); oxygen saturation \>91% on room air (dyspnea grade ≤1); left ventricular ejection fraction (lvef) ≥50% ; inr ≤1.5×uln and aptt ≤1.5×uln . 8. negative pregnancy test (blood/urine) within 7 days before car-t infusion for women of childbearing potential. all participants must agree to use effective contraception during the study and for ≥1 year post-treatment. 9. adequate venous access for leukapheresis or blood collection, with no contraindications to leukapheresis. 10. expected survival ≥3 months . exclusion criteria: 1. concurrent malignancies , except for: malignancies with disease-free survival (dfs) \>3 years ; carcinoma in situ ; 2. active viral infections : hepatitis b : positive for hbe-ab and/or hbc-ab with hbv-dna \> lower limit of quantitation (lloq) ; hepatitis c : positive hcv-ab with hcv-rna \> lloq ; positive treponema pallidum antibody (tp-ab); positive hiv antibody ; 3. uncontrolled infections (bacterial, fungal, viral, mycoplasmal, or others) as determined by the investigator; 4. clinically significant cns diseases (current or history), including: epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disorders, or cns-related autoimmune diseases , deemed uncontrolled by the investigator; 5. cardiovascular exclusion criteria : cardiac angioplasty/stent placement within 12 months prior to signing icf ; nyha class ii-iv congestive heart failure , myocardial infarction, unstable angina, or other clinically significant cardiac history; qte interval ≥480 ms (fridericia correction) or lvef \<50% at screening; 6. primary immunodeficiency ; 7. severe immediate hypersensitivity to any study drug; 8. live vaccine administration within 6 weeks prior to screening ; 9. pregnancy or lactation ; 10. active autoimmune diseases ; 11. participation in another interventional clinical trial within 30 days prior to icf signing ; 12. other conditions deemed ineligible by the investigator.

Keywords: sscart-19 relapsed or refractory b-cell lymphma il-6